Exendin-4 and sitagliptin protect kidney from ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction.
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Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (γH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01).Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01).Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury.
Affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Dapi Road, Niaosung Dist,, Kaohsiung city 83301, Taiwan. han.gung@msa.hinet.net.
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Background: This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury. Methods: Adult SD-rats (n = 48) equally divided into group 1 (sham control), group 2 (IR injury), group 3 [IR + sitagliptin 600 mg/kg at post-IR 1, 24, 48 hr)], and group 4 [IR + exendin-4 10 μm/kg at 1 hr after procedure] were sacrificed after 24 and 72 hrs (n = 6 at each time from each group) following clamping of bilateral renal pedicles for 60 minutes (groups 2-4). Results: Serum creatinine level and urine protein to creatinine ratio were highest in group 2 and lowest in group 1 (all p < 0.001) without notable differences between groups 3 and 4. Kidney injury score, expressions of inflammatory biomarkers at mRNA (MMP-9, TNF-α, IL-1β, PAI-1), protein (TNF-α, NF-κB and VCAM-1), and cellular (CD68+) levels in injured kidneys at 24 and 72 hr showed an identical pattern compared to that of creatinine level in all groups (all p < 0.0001). Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (γH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01). Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01). Conclusion: Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury. Related in: MedlinePlus |
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Figure 7: Changes in protein expressions of tumor necrotic factor (TNF)-α, nuclear factor (NF)-κB and intercellular adhesion molecule (ICAM)-1 in kidney at 24 h and 72 h after ischemia-reperfusion (IR) procedure (n = 6 at each time for each group). A and B) The analytical results of TNF-α protein expression in kidney parenchyma at 24 h (A) and 72 h (B) after IR procedure. * vs. other groups with different symbols (*, †, ‡), p < 0.01 at 24 h and 72 h, respectively. C and D) The analytical results of NF-κB protein expression in kidney parenchyma at 24 h (C) and 72 h (D) after IR procedure. * vs. other groups with different symbols (*, †, ‡), p < 0.001 at 24 h and 72 h, respectively. E and F) The analytical results of ICAM-1 protein expression in kidney parenchyma at 24 h (E) and 72 h (F) after IR procedure. * vs. other groups with different symbols (*, †, ‡), p < 0.01 at 24 h and 72 h, respectively. All statistical analyses were with one-way ANOVA followed by Bonferroni multiple comparison post hoc test. Symbols (*, †, ‡) indicate significance at the 0.05 level. SC = sham control; IR = ischemia-reperfusion; Sita = sitagliptin; Ex-4 = extendin-4. Mentions: The protein expressions of inflammatory, oxidative-stress biomarkers, and reactive oxygen species (ROS) at 24 and 72 hr after IR injury (Figures 7, 8 and 9). |
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Affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Dapi Road, Niaosung Dist,, Kaohsiung city 83301, Taiwan. han.gung@msa.hinet.net.
Background: This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury.
Methods: Adult SD-rats (n = 48) equally divided into group 1 (sham control), group 2 (IR injury), group 3 [IR + sitagliptin 600 mg/kg at post-IR 1, 24, 48 hr)], and group 4 [IR + exendin-4 10 μm/kg at 1 hr after procedure] were sacrificed after 24 and 72 hrs (n = 6 at each time from each group) following clamping of bilateral renal pedicles for 60 minutes (groups 2-4).
Results: Serum creatinine level and urine protein to creatinine ratio were highest in group 2 and lowest in group 1 (all p < 0.001) without notable differences between groups 3 and 4. Kidney injury score, expressions of inflammatory biomarkers at mRNA (MMP-9, TNF-α, IL-1β, PAI-1), protein (TNF-α, NF-κB and VCAM-1), and cellular (CD68+) levels in injured kidneys at 24 and 72 hr showed an identical pattern compared to that of creatinine level in all groups (all p < 0.0001). Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (γH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01). Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01).
Conclusion: Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury.